Journal ofthe Royal Society of Medicine Volume 72 November 1979
815
Pregnancy following renal transplantation1 V Parsons DM FRCP M Bewick Mch FRCS J Elias MD MRCOG
S A Snowden MB ChB M J Weston MD MRCP C H Rodeck Bsc MRCOG
Departments of Renal Medicine and Obstetrics,
King's College Hospital, London SE5 9RS
Introduction Chronic renal failure requiring dialysis or renal transplant therapy is usually preceded by a period of relative infertility in the male and female patient. This is the result of a combination of toxic, endocrine and general ill health which accompanies the onset of severe renal failure resulting in anaemia, hyperprolactinaemia and loss of libido (Wills 1978). Following transplantation the restoration of normal renal and endocrine function can occur quite rapidly, the hormonal abnormalities can be corrected within a matter of weeks and conception is possible within the first three months of a successful transplant. However, there is no doubt that a pregnancy in the first year following transplantation - with its more frequent rejection episodes, higher steroid dose and more frequent complications within the transplanted kidney - should be avoided, and the patient who is keen to conceive should be given appropriate contraceptive advice. The European Dialysis and Transplant Association figures for 1967-77 (Table 1) show a high incidence of surgical abortion of the transplanted Table 1. Pregnancies in transplanted and dialysed women in Europe 1967-1977
(by kind permission European Dialysis and Transplant Association Registry) Live births
Abortions
Mode of treatment
Normal child
Abnormal child
Surgical
Spontaneous
Pregnant on 31.12.77
Transplanted Dialysed
750 15
4 1
57 45
16 54
18 1
0 Includes 2 pairs of normal twins and two patients with 2 separate pregnancies
patient. This was probably due in some part to the early restoration of normal ovulation and the possibility of conception, coupled with the anxiety of the transplant surgeons and physicians that a pregnancy might complicate their management in the early months of a successful transplant. Methods Seven renal transplant patients with 9 pregnancies were cared for in the South East Thames Region over the last seven years. The patients were seen in obstetric and transplant clinics, and immunosuppression with oral prednisone and azathioprine was continued throughout pregnancy. Supplements of folic acid, iron and vitamins were given, and one patient with hypoparathyroidism received Vitamin D or la- hydroxycholecalciferol throughout pregnancy. They were seen monthly in the first two trimesters but as often as weekly in the last few weeks. Weight, blood pressure, urinary protein and oestriol were estimated regularly with the usual blood counts and electrolytes. Ultrasound in the last trimester monitored fetal growth. 1 Paper read to Section of Urology, 23 November 1978. Accepted 28 March 1979
0141-0768/79/110815-03/$01.00/0
1--"
1979 The Royal Society of Medicine
816
Journal ofthe Royal Society ofMedicine Volume 72 November 1979
Results Progress of the pregnancy was uneventful in all the patients except one who had a spontaneous abortion at ten weeks (Table 2). Two patients became pregnant within the first year of transplantation and although this was not ideal there was no question of an abortion being required for the only reason of a recent transplant. Effects on the pre-existing renal function were entirely favourable, and blood pressure was kept under control in the one hypertensive patient who became pregnant (Table 3). In the others hypertension was not a complication Table 2. Children's sex, birth weight and type ofdelivery
(of mother)
Sex
Year
Gestation
Birth weight (kg)
AW
Male
1971
34/52
2.45
Name
CH (1)
Female
1974
Birth weight percentile Labour
50
Spontaneous premature rupture membranes Induced
36/52
2.30
15
Female (2) 1978 MD (1) Spontaneous abortion at 10/52 (2) Female 1976 RS Female 1977 VM Female 1978 SS Female 1977
36/52
2.7
50
40/52 39/52 40/52 34/52
3.0 2.46 3.0 2.44
25 5 50 60
JS
34/52
3.0
92
Female
1976
Delivery
Vaginal, low forceps
Vaginal (amniotomy) Induced (PG) Vaginal
Spontaneous Vaginal, low forceps Spontaneous Vaginal Induced (PG) Vaginal Elective lower segment caesarean section Elective lower segment caesarean section
PG = prostaglandin E2 administered vaginally in tylose gel
Table 3. Complications, change in blood pressure and creatinine concentrations before and six months after delivery
Creatinine (jmol/l)
Blood pressure Name
Complications
Before
After
Before
After
AW
Cholestatic jaundice, vulval haematoma, resuture perineum
120/80
120/80
100
80-100
160/90 (bethanidine, debrisoquine) 130/90 (off drugs) 120/80 120/80 110/70 120/80 130/90 140/80
160/90 (propranolol)
110/140
150
140/80 (on methyl dopa) 120/80 120/85 110/70 110/60
250
380
100 100
100 160
80-100
80-100 120 140 130
CH (1)
(2) MD (1)
(2) RS VM SS JS
Hypocalcaemic fits post partum
140/90
100-120 80 160
and there were no incidents of pre-eclampsia, only two patients having had children prior to the onset of renal failure. Of the 8 pregnancies, 6 were delivered per vaginam and 2 by elective caesarean section, all after 34 weeks. Only one rejection episode occurred in the pregnancy period which is regarded immunologically as a protective state (Bulmer & Hancock 1977). Following delivery, mild rejection episodes occurred in 4 of the 7 patients within two months, requiring rejection therapy.
Journal of the Royal Society of Medicine Volume 72 November 1979
817
The birthweights of the children born were slightly under the mean for the patients' age and physique but had been made up to normal by three months (Table 2). In only one infant was there a slight abnormality - an inguinal hernia (which was repaired) without any other underlying congenital abnormality. Deterioration of renal function following pregnancy occurred in only one patient (CH) who had been hypertensive throughout the pregnancy. She has since received a second transplant to prevent her returning to dialysis with two young children. Complications around delivery included jaundice in one patient, which was diagnosed as benign cholestatic jaundice of pregnancy rather than induced by azathioprine or viral hepatitis; this recovered rapidly following delivery. In a second patient (RS) who had had a parathyroidectomy, the use of Vitamin D and its analogues through pregnancy enabled the patient to escape from serious hypocalcaemia, but this was a complication of delivery suggesting that the fetus did contribute some parathyroid hormone to the mother in this situation. Estimation of 25 OH Vitamin D and parathyroid hormone levels in the cord blood at delivery found them within the normal range. Discussion In this small series we have been fortunate to have avoided the complications which have been reported during pregnancy in transplanted patients. In one series 32% of the patients developed toxaemia and in several series there was a decrease in renal function during pregnancy which persisted following delivery. We seem also to have avoided the risks of the neonate which have been reported: in one series of 22 babies prematurity occurred in 45%, respiratory distress syndrome in 18%, congenital abnormalities in 14%, adrenocortical insufficiency in 9% and septicaemia in 9% (all reviewed by Makowski & Penn 1976). Other potential risks to the neonate are congenital defects and chromosomal damage caused by immunosuppression, particularly azathioprine. A recent review of cyclophosphamide-treated patients with renal failure and transplanted patients who were able to conceive showed very few chromosomal abnormalities and only one severely abnormal child in a series of 18 pregnancies (McGeown & Nevin 1978). Our experience is encouraging in that a pregnancy in a transplanted patient can be carried to term and delivered normally with little risk to the child. The possible decrease in transplant renal function following delivery needs to be clarified in a larger series. Summary A series of 7 renal transplant patients with 9 pregnancies is reported. A spontaneous abortion at 10 weeks was the only major problem. Of the other 8 pregnancies, 6 were delivered per vaginam and 2 by elective caesarean section, all after 34 weeks. The birthweights were slightly under the mean for the patients' age but had been made up to normal by three months. Only one rejection episode occurred during pregnancy. Mild rejection episodes occurred in 4 patients within two months following delivery. Acknowledgments: We are grateful to Professor Stewart Cameron at Guy's Hospital, and Dr Tony Trafford at the Royal Sussex County Hospital, for details of two patients under their care. References Buhner R & Hancock K W (1977) Clinical and Experimental Immunology 28, 302-305 McGeown M G & Nevin N C (1978) Proceedings of the European Dialysis and Transplant Association, vol 15. Ed. B H Robinson et al. Pitman Medical, Bath; pp 384-392 Makowski E L & Penn 1(1976) In: The Kidney in Pregnancy. Ed. R R de Alvarez. John Wiley, New York; pp 215227 Wills M R (1978) Metabolic Consequences of Chronic Renal Failure. HM & M, Aylesbury
815
Pregnancy following renal transplantation1 V Parsons DM FRCP M Bewick Mch FRCS J Elias MD MRCOG
S A Snowden MB ChB M J Weston MD MRCP C H Rodeck Bsc MRCOG
Departments of Renal Medicine and Obstetrics,
King's College Hospital, London SE5 9RS
Introduction Chronic renal failure requiring dialysis or renal transplant therapy is usually preceded by a period of relative infertility in the male and female patient. This is the result of a combination of toxic, endocrine and general ill health which accompanies the onset of severe renal failure resulting in anaemia, hyperprolactinaemia and loss of libido (Wills 1978). Following transplantation the restoration of normal renal and endocrine function can occur quite rapidly, the hormonal abnormalities can be corrected within a matter of weeks and conception is possible within the first three months of a successful transplant. However, there is no doubt that a pregnancy in the first year following transplantation - with its more frequent rejection episodes, higher steroid dose and more frequent complications within the transplanted kidney - should be avoided, and the patient who is keen to conceive should be given appropriate contraceptive advice. The European Dialysis and Transplant Association figures for 1967-77 (Table 1) show a high incidence of surgical abortion of the transplanted Table 1. Pregnancies in transplanted and dialysed women in Europe 1967-1977
(by kind permission European Dialysis and Transplant Association Registry) Live births
Abortions
Mode of treatment
Normal child
Abnormal child
Surgical
Spontaneous
Pregnant on 31.12.77
Transplanted Dialysed
750 15
4 1
57 45
16 54
18 1
0 Includes 2 pairs of normal twins and two patients with 2 separate pregnancies
patient. This was probably due in some part to the early restoration of normal ovulation and the possibility of conception, coupled with the anxiety of the transplant surgeons and physicians that a pregnancy might complicate their management in the early months of a successful transplant. Methods Seven renal transplant patients with 9 pregnancies were cared for in the South East Thames Region over the last seven years. The patients were seen in obstetric and transplant clinics, and immunosuppression with oral prednisone and azathioprine was continued throughout pregnancy. Supplements of folic acid, iron and vitamins were given, and one patient with hypoparathyroidism received Vitamin D or la- hydroxycholecalciferol throughout pregnancy. They were seen monthly in the first two trimesters but as often as weekly in the last few weeks. Weight, blood pressure, urinary protein and oestriol were estimated regularly with the usual blood counts and electrolytes. Ultrasound in the last trimester monitored fetal growth. 1 Paper read to Section of Urology, 23 November 1978. Accepted 28 March 1979
0141-0768/79/110815-03/$01.00/0
1--"
1979 The Royal Society of Medicine
816
Journal ofthe Royal Society ofMedicine Volume 72 November 1979
Results Progress of the pregnancy was uneventful in all the patients except one who had a spontaneous abortion at ten weeks (Table 2). Two patients became pregnant within the first year of transplantation and although this was not ideal there was no question of an abortion being required for the only reason of a recent transplant. Effects on the pre-existing renal function were entirely favourable, and blood pressure was kept under control in the one hypertensive patient who became pregnant (Table 3). In the others hypertension was not a complication Table 2. Children's sex, birth weight and type ofdelivery
(of mother)
Sex
Year
Gestation
Birth weight (kg)
AW
Male
1971
34/52
2.45
Name
CH (1)
Female
1974
Birth weight percentile Labour
50
Spontaneous premature rupture membranes Induced
36/52
2.30
15
Female (2) 1978 MD (1) Spontaneous abortion at 10/52 (2) Female 1976 RS Female 1977 VM Female 1978 SS Female 1977
36/52
2.7
50
40/52 39/52 40/52 34/52
3.0 2.46 3.0 2.44
25 5 50 60
JS
34/52
3.0
92
Female
1976
Delivery
Vaginal, low forceps
Vaginal (amniotomy) Induced (PG) Vaginal
Spontaneous Vaginal, low forceps Spontaneous Vaginal Induced (PG) Vaginal Elective lower segment caesarean section Elective lower segment caesarean section
PG = prostaglandin E2 administered vaginally in tylose gel
Table 3. Complications, change in blood pressure and creatinine concentrations before and six months after delivery
Creatinine (jmol/l)
Blood pressure Name
Complications
Before
After
Before
After
AW
Cholestatic jaundice, vulval haematoma, resuture perineum
120/80
120/80
100
80-100
160/90 (bethanidine, debrisoquine) 130/90 (off drugs) 120/80 120/80 110/70 120/80 130/90 140/80
160/90 (propranolol)
110/140
150
140/80 (on methyl dopa) 120/80 120/85 110/70 110/60
250
380
100 100
100 160
80-100
80-100 120 140 130
CH (1)
(2) MD (1)
(2) RS VM SS JS
Hypocalcaemic fits post partum
140/90
100-120 80 160
and there were no incidents of pre-eclampsia, only two patients having had children prior to the onset of renal failure. Of the 8 pregnancies, 6 were delivered per vaginam and 2 by elective caesarean section, all after 34 weeks. Only one rejection episode occurred in the pregnancy period which is regarded immunologically as a protective state (Bulmer & Hancock 1977). Following delivery, mild rejection episodes occurred in 4 of the 7 patients within two months, requiring rejection therapy.
Journal of the Royal Society of Medicine Volume 72 November 1979
817
The birthweights of the children born were slightly under the mean for the patients' age and physique but had been made up to normal by three months (Table 2). In only one infant was there a slight abnormality - an inguinal hernia (which was repaired) without any other underlying congenital abnormality. Deterioration of renal function following pregnancy occurred in only one patient (CH) who had been hypertensive throughout the pregnancy. She has since received a second transplant to prevent her returning to dialysis with two young children. Complications around delivery included jaundice in one patient, which was diagnosed as benign cholestatic jaundice of pregnancy rather than induced by azathioprine or viral hepatitis; this recovered rapidly following delivery. In a second patient (RS) who had had a parathyroidectomy, the use of Vitamin D and its analogues through pregnancy enabled the patient to escape from serious hypocalcaemia, but this was a complication of delivery suggesting that the fetus did contribute some parathyroid hormone to the mother in this situation. Estimation of 25 OH Vitamin D and parathyroid hormone levels in the cord blood at delivery found them within the normal range. Discussion In this small series we have been fortunate to have avoided the complications which have been reported during pregnancy in transplanted patients. In one series 32% of the patients developed toxaemia and in several series there was a decrease in renal function during pregnancy which persisted following delivery. We seem also to have avoided the risks of the neonate which have been reported: in one series of 22 babies prematurity occurred in 45%, respiratory distress syndrome in 18%, congenital abnormalities in 14%, adrenocortical insufficiency in 9% and septicaemia in 9% (all reviewed by Makowski & Penn 1976). Other potential risks to the neonate are congenital defects and chromosomal damage caused by immunosuppression, particularly azathioprine. A recent review of cyclophosphamide-treated patients with renal failure and transplanted patients who were able to conceive showed very few chromosomal abnormalities and only one severely abnormal child in a series of 18 pregnancies (McGeown & Nevin 1978). Our experience is encouraging in that a pregnancy in a transplanted patient can be carried to term and delivered normally with little risk to the child. The possible decrease in transplant renal function following delivery needs to be clarified in a larger series. Summary A series of 7 renal transplant patients with 9 pregnancies is reported. A spontaneous abortion at 10 weeks was the only major problem. Of the other 8 pregnancies, 6 were delivered per vaginam and 2 by elective caesarean section, all after 34 weeks. The birthweights were slightly under the mean for the patients' age but had been made up to normal by three months. Only one rejection episode occurred during pregnancy. Mild rejection episodes occurred in 4 patients within two months following delivery. Acknowledgments: We are grateful to Professor Stewart Cameron at Guy's Hospital, and Dr Tony Trafford at the Royal Sussex County Hospital, for details of two patients under their care. References Buhner R & Hancock K W (1977) Clinical and Experimental Immunology 28, 302-305 McGeown M G & Nevin N C (1978) Proceedings of the European Dialysis and Transplant Association, vol 15. Ed. B H Robinson et al. Pitman Medical, Bath; pp 384-392 Makowski E L & Penn 1(1976) In: The Kidney in Pregnancy. Ed. R R de Alvarez. John Wiley, New York; pp 215227 Wills M R (1978) Metabolic Consequences of Chronic Renal Failure. HM & M, Aylesbury
